title: Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate with a reduced risk of infection in the RV144 vaccine efficacy trial.
abstract: Neutralizing and non-neutralizing antibodies to linear epitopes on HIV-1 envelope glycoproteins have potential to mediate antiviral effector functions that could be beneficial to vaccine-induced protection. Here, plasma IgG responses were assessed in three HIV-1 gp120 vaccine efficacy trials (RV144, Vax003, Vax004) and in HIV-1-infected individuals by using arrays of overlapping peptides spanning the entire consensus gp160 of all major genetic subtypes and circulating recombinant forms (CRFs) of the virus. In RV144, where 31.2% efficacy against HIV-1 infection was seen, dominant responses targeted the C1, V2, V3 and C5 regions of gp120. An analysis of RV144 case-control samples showed that IgG to V2 CRF01_AE significantly inversely correlated with infection risk (OR= 0.54, p=0.0042), as did the response to other V2 subtypes (OR=0.60-0.63, p=0.016-0.025). The response to V3 CRF01_AE also inversely correlated with infection risk but only in vaccine recipients who had lower levels of other antibodies, especially Env-specific plasma IgA (OR=0.49, p=0.007) and neutralizing antibodies (OR=0.5, p=0.008). Responses to C1 and C5 showed no significant correlation with infection risk. In Vax003 and Vax004, where no significant protection was seen, serum IgG responses targeted the same epitopes as in RV144 with the exception of an additional C1 reactivity in Vax003 and infrequent V2 reactivity in Vax004. In HIV-1 infected subjects, dominant responses targeted the V3 and C5 regions of gp120, as well as the immunodominant domain, heptad repeat 1 (HR-1) and membrane proximal external region (MPER) of gp41. These results highlight the presence of several dominant linear B cell epitopes on the HIV-1 envelope glycoproteins. They also generate the hypothesis that IgG to linear epitopes in the V2 and V3 regions of gp120 are part of a complex interplay of immune responses that contributed to protection in RV144.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Raphael
authors.initials: R
authors.lastname: Gottardo
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.forename: S
authors.initials: S
authors.lastname: Gnanakaran
authors.forename: Joshua
authors.initials: J
authors.lastname: Phillips
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Shen
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Ellen
authors.initials: E
authors.lastname: Turk
authors.forename: Gregory
authors.initials: G
authors.lastname: Imholte
authors.forename: Larry
authors.initials: L
authors.lastname: Eckler
authors.forename: Holger
authors.initials: H
authors.lastname: Wenschuh
authors.forename: Johannes
authors.initials: J
authors.lastname: Zerweck
authors.forename: Kelli
authors.initials: K
authors.lastname: Greene
authors.forename: Hongmei
authors.initials: H
authors.lastname: Gao
authors.forename: Phillip W
authors.initials: PW
authors.lastname: Berman
authors.forename: Donald
authors.initials: D
authors.lastname: Francis
authors.forename: Faruk
authors.initials: F
authors.lastname: Sinangil
authors.forename: Carter
authors.initials: C
authors.lastname: Lee
authors.forename: Sorachai
authors.initials: S
authors.lastname: Nitayaphan
authors.forename: Supachai
authors.initials: S
authors.lastname: Rerks-Ngarm
authors.forename: Jaranit
authors.initials: J
authors.lastname: Kaewkungwal
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.forename: James
authors.initials: J
authors.lastname: Tartaglia
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Steve
authors.initials: S
authors.lastname: Self
authors.forename: Peter
authors.initials: P
authors.lastname: Gilbert
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D000939:Epitopes / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D008969:Molecular Sequence Data; D012306:Risk; D016415:Sequence Alignment
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000956:Antigens, Viral; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C514787:gp41 protein, Human immunodeficiency virus 1